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The present study was designed to test the potential utility of regional cerebral oxygen saturation (rcSO 2 ) in detecting term infants with brain injury. The study also examined whether quantitative rcSO 2 features are associated with grade of hypoxic ischaemic encephalopathy (HIE). We analysed 58 term infants with HIE (>36 weeks of gestational age) enrolled in a prospective observational study. All newborn infants had a period of continuous rcSO 2  monitoring and magnetic resonance imaging (MRI) assessment during the first week of life. rcSO 2  Signals were pre-processed and quantitative features were extracted. Machine-learning and deep-learning models were developed to detect adverse outcome (brain injury on MRI or death in the first week) using the leave-one-out cross-validation approach and to assess the association between rcSO 2 and HIE grade (modified Sarnat - at 1 h). The machine-learning model (rcSO 2 excluding prolonged relative desaturations) significantly detected infant MRI outcome or death in the first week of life [area under the curve (AUC) = 0.73, confidence interval (CI) = 0.59-0.86, Matthew's correlation coefficient = 0.35]. In agreement, deep learning models detected adverse outcome with an AUC = 0.64, CI = 0.50-0.79. We also report a significant association between rcSO 2 features and HIE grade using a machine learning approach (AUC = 0.81, CI = 0.73-0.90). We conclude that automated analysis of rcSO 2 using machine learning methods in term infants with HIE was able to determine, with modest accuracy, infants with adverse outcome. De novo approaches to signal analysis of NIRS holds promise to aid clinical decision making in the future. KEY POINTS: Hypoxic-induced neonatal brain injury contributes to both short- and long-term functional deficits. Non-invasive continuous monitoring of brain oxygenation using near-infrared- spectroscopy offers a potential new insight to the development of serious injury. In this study, characteristics of the NIRS signal were summarised using either predefined features or data-driven feature extraction, both were combined with a machine learning approach to predict short-term brain injury. Using data from a cohort of term infants with hypoxic ischaemic encephalopathy, the present study illustrates that automated analysis of regional cerebral oxygen saturation rcSO 2 , using either machine learning or deep learning methods, was able to determine infants with adverse outcome., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objective: To systematically assess decline in respiratory measures in amyotrophic lateral sclerosis (ALS) and to examine the impact of sex, disease onset type and baseline morbidity on progression., Methods: The REVEALS study (Registry of Endpoints and Validated Experiences in ALS) was conducted between April 2018 and February 2021 in six European ALS centers. Slow and forced vital capacity (S/FVC), sniff nasal inspiratory pressure (SNIP), peak cough flow, amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R), and respiratory morbidity were collected. Data were analyzed using a Bayesian multiple outcomes random effects model., Results: Two hundred and eighty participants had a median of three assessments (IQR 2.0, 5.0) over a median of 8 months (IQR 2.3, 14.1). There were 974 data collection timepoints. Differences in respiratory measures and rates of decline between disease-onset and sex subgroups were identified. Females had lower scores in all respiratory measures and females with bulbar onset ALS had faster decline compared with other sub-groups. These differences were not detected by the ALSFRS-r respiratory subscale. Dyspnea, orthopnea, and a higher King's stage at baseline were associated with lower respiratory scores throughout follow-up, while having a regular productive cough at baseline was associated with lower peak cough flow scores., Conclusion: Respiratory function declines more quickly in females with ALS compared with males when measured by FVC, SVC, SNIP, or PCF, but not the ALSFRS-R respiratory sub-score. Higher baseline King's staging and the presence of clinical respiratory symptoms at baseline were associated with worse respiratory function. The ALSFRS-R respiratory sub-score is poorly correlated with objective respiratory measurements.

Study Objectives: This study aimed to outline the strategy and outcomes of a study team in recruiting participants for an infant sleep study via social media during the COVID-19 pandemic, to assess the feasibility of recruitment via social media, and to quantitatively and qualitatively explore parental satisfaction and perceptions of recruitment via social media., Methods: The assessing sleep in infants with early-onset atopic dermatitis by longitudinal evaluation (SPINDLE) study recruited infants with and without atopic dermatitis for a longitudinal study assessing sleep. Infants were recruited via social media and their parents were interviewed to explore their experience of recruitment via social media., Results: In total, 57 controls and 33 cases were recruited. Of the 45 controls recruited via social media, 43 (95.6%) were recruited via Instagram and 2 (4.4%) were recruited via Twitter. Of the seven cases recruited via social media, 6 (85.7%) were recruited via Facebook (via sharing of Instagram posts by third parties on Facebook) and 1 (14.3%) was recruited via Instagram. All (100%, n  = 28) mothers recruited via social media who completed the full study were satisfied with this approach to recruitment. Specific reasons why mothers reported engaging following exposure to the social media posts included the benefit of additional health checks for their baby, the benefit to scientific advancement, and the opportunity for a stimulating outing following the COVID-19 lockdowns., Conclusions: Our experience highlights parents' acceptance of recruitment via social media, the optimization of time and financial resources, and the benefit of using internet-based recruitment during a pandemic., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Neonatology is a pediatric sub-discipline focused on providing care for newborn infants, including healthy newborns, those born prematurely, and those who present with illnesses or malformations requiring medical care. The European Training Requirements (ETR) in Neonatology provide a framework for standardized quality and recognition of equality of training throughout Europe. The latest ETR version was approved by the Union of European Medical Specialists (UEMS) in April 2021. Here, we present the curriculum of the European School of Neonatology Master of Advanced Studies (ESN MAS), which is based on the ETR in Neonatology and aims to provide a model for effective and standardized training and education in neonatal medicine. We review the history and theory that form the foundation of contemporary medical education and training, provide a literature review on best practices for medical training, pediatric training, and neonatology training specifically, including educational frameworks and evidence-based systems of evaluation. The ESN MAS Curriculum is then evaluated in light of these best practices to define its role in meeting the need for a standardized empirically supported neonatology training curriculum for physicians, and in the future for nurses, to improve the quality of neonatal care for all infants. IMPACT STATEMENT: A review of the neonatology training literature was conducted, which concluded that there is a need for standardized neonatology training across international contexts to keep pace with growth in the field and rapidly advancing technology. This article presents the European School of Neonatology Master of Advanced Studies in Neonatology, which is intended to provide a standardized training curriculum for pediatricians and nurses seeking sub-specialization in neonatology. The curriculum is evaluated in light of best practices in medical education, neonatology training, and adult learning theory., (© 2024. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) pandemic impacted cancer services worldwide. We examined the effect of the first three pandemic waves on the number of electronic (e)-referrals to rapid access clinics (RACs) for breast, lung and prostate cancer in Ireland., Methods: This study used a retrospective, repeated cross-sectional design. The predicted weekly number of e-referrals by suspected cancer types from March 2020 to May 2021 was calculated using the Holt-Winters seasonal smoothing method, based on the observed numbers from a representative pre-pandemic period (01 January 2019 to 01 March 2020) and compared this with the observed number across the first three pandemic waves (02 March 2020 to 09 May 2021). Percentage differences were calculated between observed and predicted numbers of e-referrals for the three RACs and patterns were examined in each wave., Results: Observed e-referrals were lower than predicted for all three RACs in the first wave of the pandemic (15.7% lower for breast, 39.5% lower for lung and 28.1% lower for prostate) with varying levels of recovery in the second and third waves for the three e-referral types., Conclusions: The COVID-19 pandemic impacted patterns of e-referrals to RACs in the first three pandemic waves in Ireland. Early identification of changes in engagement with health services, such as a decrease in primary care presentations with a resultant decrease in e-referrals to RACs can allow for a rapid response from cancer control programmes. Continued surveillance of the impact of service disruption on cancer services allows policy makers and strategic leaders in cancer control programmes to respond rapidly to mitigate the impact on cancer outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Objective: To validate a hypoxic ischaemic encephalopathy (HIE) prediction algorithm to identify infants at risk of HIE immediately after birth using readily available clinical data., Design: Secondary review of electronic health record data of term deliveries from January 2017 to December 2021., Setting: A tertiary maternity hospital., Patients: Infants >36 weeks' gestation with the following clinical variables available: Apgar Score at 1 min and 5 min, postnatal pH, base deficit, and lactate values taken within 1 hour of birth INTERVENTIONS: Previously trained open-source logistic regression and random forest (RF) prediction algorithms were used to calculate a probability index (PI) for each infant for the occurrence of HIE., Main Outcome: Validation of a machine learning algorithm to identify infants at risk of HIE in the immediate postnatal period., Results: 1081 had a complete data set available within 1 hour of birth: 76 (6.95%) with HIE and 1005 non-HIE. Of the 76 infants with HIE, 37 were classified as mild, 29 moderate and 10 severe. The best overall accuracy was seen with the RF model. Median (IQR) PI in the HIE group was 0.70 (0.53-0.86) vs 0.05 (0.02-0.15), (p<0.001) in the non-HIE group. The area under the receiver operating characteristics curve for prediction of HIE=0.926 (0.893-0.959, p<0.001). Using a PI cut-off to optimise sensitivity of 0.30, 936 of the 1081 (86.5%) infants were correctly classified., Conclusion: In a large unseen data set an open-source algorithm could identify infants at risk of HIE in the immediate postnatal period. This may aid focused clinical examination, transfer to tertiary care (if necessary) and timely intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Electroencephalography (EEG) is a key objective biomarker of newborn brain function, delivering critical, cotside insights to aid the management of encephalopathy. Access to continuous EEG is limited, forcing reliance on subjective clinical assessments. In hypoxia ischaemia, the primary cause of encephalopathy, alterations in EEG patterns correlate with. injury severity and evolution. As HIE evolves, causing secondary neuronal death, EEG can track injury progression, informing neuroprotective strategies, seizure management and prognosis. Despite its value, challenges with interpretation and lack of on site expertise has limited its broader adoption. Technological advances, particularly in digital EEG and machine learning, are enhancing real-time analysis. This will allow EEG to expand its role in HIE diagnosis, management and outcome prediction., Competing Interests: Disclosure D.M. Murray is the founder of Liltoda Ltd. G.B. Boylan has a consultancy with Nihon Kohden; she is co-founder of Kephala Ltd and CergenX Ltd. J.M. O'Toole is an employee of CergenX Ltd., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To estimate net survival and cancer cure fraction (CF), i.e. the proportion of patients no longer at risk of dying from cancer progression/relapse, a clear distinction needs to be made between mortality from cancer and from other causes. Conventionally, CF is estimated assuming no excess mortality compared to the general population., Methods: A new modelling approach, that corrects for patients' extra risk of dying (RR) from causes other than the diagnosed cancer, was considered to estimate both indicators. We analysed EUROCARE-6 data on head and neck (H&N), colorectal, and breast cancer patients aged 40-79, diagnosed from 1998 to 2002 and followed-up to 31/12/2014, provided by 65 European cancer registries., Findings: Young male H&N cancer patients have 4 times the risk of dying from other causes than their peers, this risk decreases with age to 1.6. Similar results were observed for female. We observed an absolute increase in CF of 30 % using the new model instead of the conventional one. For colorectal cancer, CF with the new model increased by a maximum of 3 % for older patients and the RR ranged from 1 to 1.2 for both sexes. CF of female breast cancer ranged from 73 % to 79 % using the new cure model, with RR between 1.2 and 1.4., Interpretation: Not considering a RR> 1 leads to underestimate the proportion of patients not bound to die of their diagnosed cancer. Estimates of cancer mortality risk have an important impact on patients' quality of life., Competing Interests: Declaration of Competing Interest The sponsor have no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

To achieve a single fully harmonised research data set suitable for analysis from data collected at multiple sites requires not only semantic integration of collection concepts and convergence onto single collection units, but harmonisation of data collection processes. We describe our experience of identifying harmonisation challenges in the Precision ALS project, with particular focus on process alignment challenges in a multi-site multi-national research data collection project.

Background: The healthcare system in Ireland was profoundly affected by COVID-19. This study aimed to explore the impact of the pandemic on cancer surgery in Ireland, from 2019 to 2022 using three national health data sources., Methods: A repeated cross-sectional study design was used and included: (i) cancer resections from the National Histopathology Quality Improvement (NHQI) Programmes; (ii) cancer surgery from the National Cancer Registry Ireland (NCRI), and (iii) cancer surgery from Hospital Inpatient Enquiry (HIPE) System. Cancer surgery was presented by invasive/in situ and invasive only cancers (NCRI & HIPE), and by four main cancer types (breast, lung, colorectal & melanoma for NCRI & HIPE data only)., Results: The annual number of cancer resections (NHQI) declined by 4.4% in 2020 but increased by 4% in 2021 compared with 2019. NCRI data indicated invasive/in-situ cancer surgery for the four main cancer types declined by 14% in 2020 and 5.1% in 2021, and by 12.3% and 7.3% for invasive cancer only, compared to 2019. Within HIPE for the same tumour types, invasive/in situ cancer surgery declined by 21.9% in 2020 and 9.9% in 2021 and by 20.8% and 9.6% for invasive cancer only. NHQI and HIPE data indicated an increase in the number of cancer surgeries performed in 2022., Conclusions: Cancer surgery declined in the initial pandemic waves suggests mitigation measures for cancer surgery, including utilising private hospitals for public patients, reduced the adverse impact on cancer surgery., Competing Interests: All authors have no conflict of interest. KB is in receipt of funding from IQVIA and Novartis for unrelated research projects., (© 2024 The Authors.)

Background: 'Neonatal encephalopathy' (NE) describes a group of conditions in term infants presenting in the earliest days after birth with disturbed neurological function of cerebral origin. NE is aetiologically heterogenous; one cause is peripartum hypoxic ischaemia. Lack of uniformity in the terminology used to describe NE and its diagnostic criteria creates difficulty in the design and interpretation of research and complicates communication with families. The DEFINE study aims to use a modified Delphi approach to form a consensus definition for NE, and diagnostic criteria., Methods: Directed by an international steering group, we will conduct a systematic review of the literature to assess the terminology used in trials of NE, and with their guidance perform an online Real-time Delphi survey to develop a consensus diagnosis and criteria for NE. A consensus meeting will be held to agree on the final terminology and criteria, and the outcome disseminated widely., Discussion: A clear and consistent consensus-based definition of NE and criteria for its diagnosis, achieved by use of a modified Delphi technique, will enable more comparability of research results and improved communication among professionals and with families., Impact: The terms Neonatal Encephalopathy and Hypoxic Ischaemic Encephalopathy tend to be used interchangeably in the literature to describe a term newborn with signs of encephalopathy at birth. This creates difficulty in communication with families and carers, and between medical professionals and researchers, as well as creating difficulty with performance of research. The DEFINE project will use a Real-time Delphi approach to create a consensus definition for the term 'Neonatal Encephalopathy'. A definition formed by this consensus approach will be accepted and utilised by the neonatal community to improve research, outcomes, and parental experience., (© 2024. The Author(s).)

Background: There are no early, accurate, scalable methods for identifying infants at high risk of poor cognitive outcomes in childhood. We aim to develop an explainable predictive model, using machine learning and population-based cohort data, for this purpose., Methods: Data were from 8858 participants in the Growing Up in Ireland cohort, a nationally representative study of infants and their primary caregivers (PCGs). Maternal, infant, and socioeconomic characteristics were collected at 9-months and cognitive ability measured at age 5 years. Data preprocessing, synthetic minority oversampling, and feature selection were performed prior to training a variety of machine learning models using ten-fold cross validated grid search to tune hyperparameters. Final models were tested on an unseen test set., Results: A random forest (RF) model containing 15 participant-reported features in the first year of infant life, achieved an area under the receiver operating characteristic curve (AUROC) of 0.77 for predicting low cognitive ability at age 5. This model could detect 72% of infants with low cognitive ability, with a specificity of 66%., Conclusions: Model performance would need to be improved before consideration as a population-level screening tool. However, this is a first step towards early, individual, risk stratification to allow targeted childhood screening., Impact: This study is among the first to investigate whether machine learning methods can be used at a population-level to predict which infants are at high risk of low cognitive ability in childhood. A random forest model using 15 features which could be easily collected in the perinatal period achieved an AUROC of 0.77 for predicting low cognitive ability. Improved predictive performance would be required to implement this model at a population level but this may be a first step towards early, individual, risk stratification., (© 2024. The Author(s).)

Introduction: Cyberattacks represent a growing threat for healthcare delivery globally. We assess the impact and implications of a cyberattack on a cancer center in Ireland., Methods: On May 14th 2021 (day 0) Cork University Hospital (CUH) Cancer Center was involved in the first national healthcare ransomware attack in Ireland. Contingency plans were only present in laboratory services who had previously experienced information technology (IT) failures. No hospital cyberattack emergency plan was in place. Departmental logs of activity for 120 days after the attack were reviewed and compared with historical activity records. Daily sample deficits (routine daily number of samples analyzed - number of samples analyzed during cyberattack) were calculated. Categorical variables are reported as median and range. Qualitative data were collected via reflective essays and interviews with key stakeholders from affected departments in CUH., Results: On day 0, all IT systems were shut down. Radiotherapy (RT) treatment and cancer surgeries stopped, outpatient activity fell by 50%. hematology, biochemistry and radiology capacity fell by 90% (daily sample deficit (DSD) 2700 samples), 75% (DSD 2250 samples), and 90% (100% mammography/PET scan) respectively. Histopathology reporting times doubled (7 to 15 days). Radiotherapy (RT) was interrupted for 113 patients in CUH. The median treatment gap duration was six days for category 1 patients and 10 for the remaining patients. Partner organizations paused all IT links with CUH. Outsourcing of radiology and radiotherapy commenced, alternative communication networks and national conference calls in RT and Clinical Trials were established. By day 28 Email communication was restored. By day 210 reporting and data storage backlogs were cleared and over 2000 computers were checked/replaced., Conclusion: Cyberattacks have rapid, profound and protracted impacts. While laboratory and diagnostic deficits were readily quantified, the impact of disrupted/delayed care on patient outcomes is less readily quantifiable. Cyberawareness and cyberattack plans need to be embedded in healthcare., Policy Summary: Cyberattacks pose significant challenges for healthcare systems, impacting patient care, clinical outcomes, and staff wellbeing. This study provides a comprehensive review of the impact of the Conti ransomware attack on cancer services in Cork University Hospital (CUH), the first cyberattack on a national health service. Our study highlights the widespread disruption caused by a cyberattack including shutdown of information technology (IT) services, marked reduction in outpatient activity, temporary cessation of essential services such as radiation therapy. We provide a framework for other institutions for mitigating the impact of a cyberattack, underscoring the need for a cyberpreparedness plan similar to those made for natural disasters and the profound legacy of a cyberattack on patient care., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Despite extensive research on neonatal hypoxic-ischaemic encephalopathy, detailed information about electrographic seizures during active cooling and rewarming of therapeutic hypothermia is sparse. We aimed to describe temporal evolution of seizures and determine whether there is a correlation of seizure evolution with 2-year outcome., Methods: This secondary analysis included newborn infants recruited from eight European tertiary neonatal intensive care units for two multicentre studies (a randomised controlled trial [NCT02431780] and an observational study [NCT02160171]). Infants were born at 36 +0 weeks of gestation with moderate or severe hypoxic-ischaemic encephalopathy and underwent therapeutic hypothermia with prolonged conventional video-electroencephalography (EEG) monitoring for 10 h or longer from the start of rewarming. Seizure burden characteristics were calculated based on electrographic seizures annotations: hourly seizure burden (minutes of seizures within an hour) and total seizure burden (minutes of seizures within the entire recording). We categorised infants into those with electrographic seizures during active cooling only, those with electrographic seizures during cooling and rewarming, and those without seizures. Neurodevelopmental outcomes were determined using the Bayley's Scales of Infant and Toddler Development, Third Edition (BSID-III), the Griffiths Mental Development Scales (GMDS), or neurological assessment. An abnormal outcome was defined as death or neurodisability at 2 years. Neurodisability was defined as a composite score of 85 or less on any subscales for BSID-III, a total score of 87 or less for GMDS, or a diagnosis of cerebral palsy (dyskinetic cerebral palsy, spastic quadriplegia, or mixed motor impairment) or epilepsy., Findings: Of 263 infants recruited between Jan 1, 2011, and Feb 7, 2017, we included 129 infants: 65 had electrographic seizures (43 during active cooling only and 22 during and after active cooling) and 64 had no seizures. Compared with infants with seizures during active cooling only, those with seizures during and after active cooling had a longer seizure period (median 12 h [IQR 3-28] vs 68 h [35-86], p<0·0001), more seizures (median 12 [IQR 5-36] vs 94 [24-134], p<0·0001), and higher total seizure burden (median 69 min [IQR 22-104] vs 167 min [54-275], p=0·0033). Hourly seizure burden peaked at about 20-24 h in both groups, and infants with seizures during and after active cooling had a secondary peak at 85 h of age. When combined, worse EEG background (major abnormalities and inactive background) at 12 h and 24 h were associated with the seizure group: compared with infants with a better EEG background (normal, mild, or moderate abnormalities), infants with a worse EEG background were more likely to have seizures after cooling at 12 h (13 [54%] of 24 vs four [14%] of 28; odds ratio 7·09 [95% CI 1·88-26·77], p=0·0039) and 24 h (14 [56%] of 25 vs seven [18%] of 38; 5·64 [1·81-17·60], p=0·0029). There was a significant relationship between EEG grade at 12 h (four categories) and seizure group (p=0·020). High total seizure burden was associated with increased odds of an abnormal outcome at 2 years of age (odds ratio 1·007 [95% CI 1·000-1·014], p=0·046), with a medium negative correlation between total seizure burden and BSID-III cognitive score (r S =-0·477, p=0·014, n=26)., Interpretation: Overall, half of infants with hypoxic-ischaemic encephalopathy had electrographic seizures and a third of those infants had seizures beyond active cooling, with worse outcomes. These results raise the importance of prolonged EEG monitoring of newborn infants with hypoxic-ischaemic encephalopathy not only during active cooling but throughout the rewarming phase and even longer when seizures are detected., Funding: Wellcome Trust, Science Foundation Ireland, and the Irish Health Research Board., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of the study was to evaluate neuronal injury and immuno-inflammatory biomarkers in umbilical cord blood (UCB) at birth, in cases with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE), compared with healthy controls and to assess their ability to predict HIE., Study Design: In this case-control study, term infants with perinatal asphyxia were recruited at birth. UCB was stored at delivery for batch analysis. HIE was diagnosed by clinical Sarnat staging at 24 h. Glial fibrillary acidic protein (GFAP), the neuronal biomarkers tau and neurofilament light protein (NFL), and a panel of cytokines were analyzed in a total of 150 term neonates: 50 with HIE, 50 with asphyxia without HIE (PA), and 50 controls. GFAP, tau, and NFL concentrations were measured using ultrasensitive single-molecule array (Simoa) assays, and a cytokine screening panel was applied to analyze the immuno-inflammatory and infectious markers., Results: GFAP, tau, NFL, and several cytokines were significantly higher in newborns with moderate and severe HIE compared to a control group and provided moderate prediction of HIE II/III (AUC: 0.681-0.827). Furthermore, the levels of GFAP, tau, interleukin-6 (IL-6), and interleukin-8 (IL-8) were higher in HIE II/III cases compared with cases with PA/HIE I. IL-6 was also higher in HIE II/III compared with HIE I cases., Conclusions: Biomarkers of brain injury and inflammation were increased in umbilical blood in cases with asphyxia. Several biomarkers were higher in HIE II/III versus those with no HIE or HIE I, suggesting that they could assist in the prediction of HIE II/III., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Importance: Early intervention can improve cognitive outcomes for very preterm infants but is resource intensive. Identifying those who need early intervention most is important., Objective: To evaluate a model for use in very preterm infants to predict cognitive delay at 2 years of age using routinely available clinical and sociodemographic data., Design, Setting, and Participants: This prognostic study was based on the Swedish Neonatal Quality Register. Nationwide coverage of neonatal data was reached in 2011, and registration of follow-up data opened on January 1, 2015, with inclusion ending on September 31, 2022. A variety of machine learning models were trained and tested to predict cognitive delay. Surviving infants from neonatal units in Sweden with a gestational age younger than 32 weeks and complete data for the Bayley Scales of Infant and Toddler Development, Third Edition cognitive index or cognitive scale scores at 2 years of corrected age were assessed. Infants with major congenital anomalies were excluded., Exposures: A total of 90 variables (containing sociodemographic and clinical information on conditions, investigations, and treatments initiated during pregnancy, delivery, and neonatal unit admission) were examined for predictability., Main Outcomes and Measures: The main outcome was cognitive function at 2 years, categorized as screening positive for cognitive delay (cognitive index score <90) or exhibiting typical cognitive development (score ≥90)., Results: A total of 1062 children (median [IQR] birth weight, 880 [720-1100] g; 566 [53.3%] male) were included in the modeling process, of whom 231 (21.8%) had cognitive delay. A logistic regression model containing 26 predictive features achieved an area under the receiver operating curve of 0.77 (95% CI, 0.71-0.83). The 5 most important features for cognitive delay were non-Scandinavian family language, prolonged duration of hospitalization, low birth weight, discharge to other destination than home, and the infant not receiving breastmilk on discharge. At discharge from the neonatal unit, the full model could correctly identify 605 of 650 infants who would have cognitive delay at 24 months (sensitivity, 0.93) and 1081 of 2350 who would not (specificity, 0.46)., Conclusions and Relevance: The findings of this study suggest that predictive modeling in neonatal care could enable early and targeted intervention for very preterm infants most at risk for developing cognitive impairment.

Background: Of the 15 million preterm births that occur worldwide each year, approximately 80% occur between 32 and 36 + 6 weeks gestational age (GA) and are defined as moderate to late preterm (MLP) infants. This percentage substantiates a need for a better understanding of the neurodevelopmental outcome of this group., Aim: To describe neurodevelopmental outcome at 18 months in a cohort of healthy low-risk MLP infants admitted to the neonatal unit at birth and to compare the neurodevelopmental outcome to that of a healthy term-born infant group., Study Design and Method: This single-centre observational study compared the neurodevelopmental outcome of healthy MLP infants to a group of healthy term control (TC) infants recruited during the same period using the Griffith's III assessment at 18 months., Results: Seventy-five MLP infants and 92 TC infants were included. MLP infants scored significantly lower in the subscales: Eye-hand coordination (C), Personal, Social and Emotional Development (D), Gross Motor Development (E) and General Developmental (GD) ( p  < 0.001 for each) and Foundations of Learning (A), ( p  = 0.004) in comparison to the TC infant group with Cohen's d effect sizes ranging from 0.460 to 0.665. There was no statistically significant difference in mean scores achieved in subscale B: Language and Communication between groups ( p  = 0.107)., Conclusion: MLP infants are at risk of suboptimal neurodevelopmental outcomes. Greater surveillance of the neurodevelopmental trajectory of this group of at-risk preterm infants is required., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2023 Ryan, Murray, Dempsey, Mathieson, Livingstone and Boylan.)

Background: Paediatric obesity is a global public health issue. Prenatal maternal mental health is potentially implicated in the development of childhood obesity. This study examined associations between prenatal maternal cortisol, self-reported stress, anxiety and depression in the second trimester, and childhood overweight and obesity at 5 years of age., Methods: A nested case-control study was conducted using data from the Irish prospective longitudinal birth cohort SCOPE BASELINE. Cases were children with overweight or obesity, operationalised as having a BMI z-score above +2 standard deviations. Controls were children with a BMI z-score between -0.5 and 0.5 standard deviations at 5 years of age. Two to one matching by sex was conducted. Thirty-eight cases and 83 sex-matched controls were included. Maternal serum cortisol concentration and self-reported stress, anxiety and depression were measured at 15 ± 1 and 20 ± 1 weeks gestation. Conditional logistic regression analyses were conducted to examine associations between prenatal maternal cortisol and self-reported stress, anxiety and depression, and childhood overweight and obesity., Results: Despite some evidence for associations between anxiety and depression, and child BMI z-scores in univariate analyses, adjusted models indicated no associations between prenatal maternal stress (OR: 1.02, 95% CI: 0.94-1.12), anxiety (OR: 1.03, 95% CI: 0.97-1.09), depression (OR: 1.04, 95% CI: 0.91-1.19), or cortisol concentration (OR: 0.99, 95% CI: 0.99-1.00) and child BMI z-score., Conclusion: Our findings do not provide support for associations between foetal exposure during the second trimester of pregnancy and maternal cortisol, stress and anxiety, and childhood overweight or obesity at 5 years of age.

Background: Status epilepticus is the most common neurological emergency presenting to pediatric emergency departments. Nonconvulsive status epilepticus can be extremely challenging to diagnose, however, requiring electroencephalographic (EEG) confirmation for definitive diagnosis. We aimed to determine the feasibility of achieving a good-quality pediatric EEG recording within 20 minutes of presentation to the emergency department., Methods: Single-center prospective feasibility study in Cork University Hospital, Ireland, between July 2021 and June 2022. Two-channel continuous EEG was recorded from children (1) aged <16 years and (2) with Glasgow Coma Scale <11 or a reduction in baseline Glasgow Coma Scale in the case of a child with a neurodisability., Results: Twenty patients were included. The median age at presentation was 65.8 months (interquartile range, 23.2 to 119.0); 50% had a background diagnosis of epilepsy. The most common reason for EEG monitoring was status epilepticus (85%) followed by suspected nonconvulsive status (10%) and reduced consciousness of unknown etiology (5%). The mean length of recording was 93.1 minutes (S.D. 47.4). The mean time to application was 41.3 minutes (S.D. 11.7). The mean percent of artifact in all recordings was 19.3% (S.D. 15.9). Thirteen (65%) EEGs had <25% artifact. Artifact was higher in cases in which active airway management was ongoing., Conclusions: EEG monitoring can be achieved in a pediatric emergency department setting within one hour of presentation. Overall, artifact percentage was low outside of periods of airway manipulation. Future studies are required to determine its use in early seizure detection and its support role in clinical decision-making in these patients., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Early detection of cognitive disability is challenging. We assessed the domain-specific, concurrent validity of the ages and stages questionnaire (ASQ-3) and the Bayley Scales of Infant and Toddler Development (BSID-III), and their ability to predict cognitive delay at school age., Methods: Within a longitudinal birth cohort study, a nested cohort of children was assessed using ASQ-3 and BSID-III at 24 months, and at 5 years using the Kaufmann brief IQ test (KBIT)., Results: 278 children were assessed using BSID-III and ASQ-3 at 24-months; mean(SD) BW = 3445(506) grams, M:F ratio=52:48. ASQ-3 had reasonable predictive ability (AUROC, p value, sensitivity:specificity) of same domain delay for motor (0.630, p = 0.008, 50%:76.1%) and language (0.623, p = 0.010, 25%:99.5%) at 2 years, but poor ability to detect cognitive delay compared to BSID-III (0.587, p = 0.124, 20.7%/96.8%;). 204/278 children were assessed at 5 years. BSID-III language and cognition domains showed better correlation with verbal and nonverbal IQ (R = 0.435, p < 0.001 and 0.388, p < 0.001 respectively). Both assessments showed high specificity and low sensitivity for predicting delay at 5 years., Conclusions: The ASQ-3 cognitive domain showed poor concurrent validity with BSID-III cognitive score. Both ASQ-3 and BSID-III at 2 years poorly predict cognitive delay at 5 years., Impact: The ASQ-3 does not adequately detect cognitive delay or predict cognitive delay at 5 years, particularly for children with mild to moderate delay. The ASQ-3 shows reasonable concurrent validity with the motor and language subscales of the BSID-III. Neither early screening nor formal developmental testing demonstrated significant predictive validity to screen for cognitive delay at school age. This article highlights the need to analyse our existing model of using the ASQ-3 to screen for cognitive delay in children aged 2 years., (© 2023. The Author(s).)

Introduction: The CORAL (Impact of Corona Virus Pandemic on Allergic and Autoimmune Dysregulation in Infants Born During Lockdown) study reported a reduction in social communication milestones in 12-month-old infants born into the COVID-19 pandemic., Aims: To look at 24-month developmental and behavioural outcomes in the CORAL cohort., Design: The CORAL study is a longitudinal prospective observational study of Irish infants born in the first 3 months of the pandemic. At 24 months of age, the Ages and Stages Developmental Questionnaire (ASQ24) and the Child Behaviour Checklist (CBCL) were completed and compared with prepandemic BASELINE (Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Impact) cohort., Results: 917 babies (312 CORAL infants and 605 BASELINE infants) were included. At 24 months of age, infants in the CORAL and BASELINE cohorts had similar developmental ASQ24 scores in fine motor, problem solving and personal and social domains but ASQ24 communication scores were significantly lower in the CORAL group compared with the BASELINE cohort (mean (SD) 49.5 (15.1) vs 53.7 (11.6), p<0.01). Infants from the CORAL cohort were more likely to score below standardised cut-offs for developmental concern in the communication domain (11.9% CORAL compared with 5.4% BASELINE, p<0.01). Unadjusted ASQ24 gross motor scores were lower for the pandemic cohort. Fewer CORAL infants fell under 2 SD cut-off in personal-social subdomain. For CBCL, there was no evidence of difference in scores between the cohorts on multivariable analysis., Conclusion: 24-month-old pandemic-born infants had largely similar developmental and behavioural scores compared with their prepandemic counterparts. Concerns have been raised in the communication developmental domain., Competing Interests: Competing interests: JH is director of Clemens von Pirquet Foundation., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To examine the impact of parent-led massage on the sleep electroencephalogram (EEG) features of typically developing term-born infants at 4 months., Method: Infants recruited at birth were randomized to intervention (routine parent-led massage) and control groups. Infants had a daytime sleep EEG at 4 months and were assessed using the Griffiths Scales of Child Development, Third Edition at 4 and 18 months. Comparative analysis between groups and subgroup analysis between regularly massaged and never-massaged infants were performed. Groups were compared for sleep stage, sleep spindles, quantitative EEG (primary analysis), and Griffiths using the Mann-Whitney U test., Results: In total, 179 out of 182 infants (intervention: 83 out of 84; control: 96 out of 98) had a normal sleep EEG. Median (interquartile range) sleep duration was 49.8 minutes (39.1-71.4) (n = 156). A complete first sleep cycle was seen in 67 out of 83 (81%) and 72 out of 96 (75%) in the intervention and control groups respectively. Groups did not differ in sleep stage durations, latencies to sleep and to rapid eye movement sleep. Sleep spindle spectral power was greater in the intervention group in main and subgroup analyses. The intervention group showed greater EEG magnitudes, and lower interhemispherical coherence on subgroup analyses. Griffiths assessments at 4 months (n = 179) and 18 months (n = 173) showed no group differences in the main and subgroup analyses., Interpretation: Routine massage is associated with distinct functional brain changes at 4 months., What This Paper Adds: Routine massage of infants is associated with differences in sleep electroencephalogram biomarkers at 4 months. Massaged infants had higher sleep spindle spectral power, greater sleep EEG magnitudes, and lower interhemispherical coherence. No differences between groups were observed in total nap duration or first cycle macrostructure., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Background: Young children have high nutritional requirements relative to their body size, making healthy diets critical for normal growth and development., Objective: We aimed to integrate analysis of dietary patterns among 2-y-old children with indicators of dietary quality, micronutrient status, and body weight status., Methods: Data from the 2-y follow-up of the Cork BASELINE Birth Cohort included dietary assessment using a 2-d weighed food diary, vitamin D and iron status biomarkers, and anthropometry (n = 468). K-means cluster analysis identified predominant dietary patterns based on energy contributions and associations with nutrient intakes and status and body weight were investigated., Results: Four dietary patterns emerged: "Cows' milk" (unmodified cows' milk: 32% of total energy (TE)); "Traditional" (wholemeal breads, butter, fresh meat, fruit); "Low Nutrient Density (LND) foods" (confectionary, processed meat, convenience foods) and "Formula" (young child formula: 23%TE). The LND pattern was associated with excessive free sugar intake (14%TE) and salt intake (153% of daily limit). No differences in patterns of overweight were observed between the 4 groups; however, the LND group had 3-fold higher odds of being underweight [aOR (95% CI): 3.2 (1.2, 8.5)]. Children consuming >400ml/d of cows' milk or formula exhibited lower dietary variety, fewer family-type meals, and continued use of feeding bottles (75% and 81%, respectively, vs. 35-37% in the other groups)., Conclusions: Unhealthy eating habits are common among young children. Dietary guidance to support families to provide healthy diets needs to maintain currency with eating habits and focus on food choices for meals, snacks, and beverages., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: To validate a touchscreen assessment as a screening tool for mild cognitive delay in typically developing children aged 24 months., Method: Secondary analysis of data was completed from an observational birth cohort study (The Cork Nutrition & Microbiome Maternal-Infant Cohort Study [COMBINE]), with children born between 2015 and 2017. Outcome data were collected at 24 months of age, at the INFANT Research Centre, Ireland. Outcomes were the Bayley Scales of Infant and Toddler Development, Third Edition cognitive composite score and a language-free, touchscreen-based cognitive measure (Babyscreen)., Results: A total of 101 children (47 females, 54 males) aged 24 months (mean = 24.25, SD = 0.22) were included. Cognitive composite scores correlated with the total number of Babyscreen tasks completed, with moderate concurrent validity (r = 0.358, p < 0.001). Children with cognitive composite scores lower than 90 (1 SD below the mean, defined as mild cognitive delay) had lower mean Babyscreen scores than those with cognitive scores equal to or greater than 90 (8.50 [SD = 4.89] vs 12.61 [SD = 3.68], p = 0.001). The area under the receiver operating characteristic curve for the prediction of a cognitive composite score less than 90 was 0.75 (95% confidence interval = 0.59-0.91; p = 0.006). Babyscreen scores less than 7 were equivalent to less than the 10th centile and identified children with mild cognitive delay with 50% sensitivity and 93% specificity., Interpretation: Our 15-minute, language-free touchscreen tool could reasonably identify mild cognitive delay among typically developing children., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative condition. Despite significant advances in pre-clinical models that enhance understanding of disease pathobiology, translation of candidate drugs to effective human therapies has been disappointing. There is increasing recognition of the need for a precision medicine approach toward drug development, as many failures in translation can be attributed in part to disease heterogeneity in humans. PRECISION-ALS is an academic industry collaboration between clinicians, Computer Scientists, Information engineers, technologists, data scientists and industry partners that will address the key clinical, computational, data science and technology associated research questions to generate a sustainable precision medicine based approach toward new drug development. Using extant and prospectively collected population based clinical data across nine European sites, PRECISION-ALS provides a General Data Protection Regulation (GDPR) compliant framework that seamlessly collects, processes and analyses research-quality multimodal and multi-sourced clinical, patient and caregiver journey, digitally acquired data through remote monitoring, imaging, neuro-electric-signaling, genomic and biomarker datasets using machine learning and artificial intelligence. PRECISION-ALS represents a first-in-kind modular transferable pan-European ICT framework for ALS that can be easily adapted to other regions that face similar precision medicine related challenges in multimodal data collection and analysis.

Background: Skin barrier dysfunction is a key component of the pathogenesis of atopic dermatitis (AD). Recent research on barrier optimization to prevent AD has shown mixed results. The aim of this study was to assess the relationship between emollient bathing at 2 months and the trajectory of AD in the first 2 years of life in a large unselected observational birth cohort study., Methods: The Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints Birth Cohort study enrolled 2183 infants. Variables extracted from the database related to early skincare, skin barrier function, parental history of atopy, and AD outcomes. Statistical analysis was performed to adjust for potential confounding variables., Results: One thousand five hundred five children had data on AD status available at 6, 12, and 24 months. Prevalence of AD was 18.6% at 6 months, 15.2% at 12 months, and 16.5% at 24 months. Adjusted for potential confounding variables, the odds of AD at any point were higher among infants who had emollient baths at 2 months (OR (95% CI): 2.41 (1.56 to 3.72), p < .001). Following multivariable analysis, the odds of AD were higher among infants who had both emollient baths and frequent emollient application at 2 months, compared with infants who had neither (OR (95% CI) at 6 months 1.74 (1.18-2.58), p = .038), (OR (95% CI) at 12 months 2.59 (1.69-3.94), p < .001), (OR (95% CI) at 24 months 1.87 (1.21-2.90), p = .009)., Conclusion: Early emollient bathing was associated with greater development of AD by 2 years of age in this population-based birth cohort study., (© 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Solid organ transplant recipients are recognized to carry a high burden of malignancy and frequently this cancer develops in the head and neck region. Furthermore, cancer of the head and neck post-transplant carries a significantly increased mortality. In this study, we aim to conduct a national retrospective cohort study to investigate the impact of head and neck cancer in terms of frequency and mortality in a large group of solid organ transplant recipients over a 20 year time span and compare the mortality in transplant patients to non-transplant patients with head and neck cancer., Methods: Patients in the Republic of Ireland who underwent solid organ transplantation between 1994 and 2014 who developed post-transplant head and neck malignancy were identified from the records of two prospective, national databases (National Cancer Registry of Ireland (NCRI) and The Irish Transplant Cancer Group database) working in conjunction with each other. Incidence of head and neck malignancy post-transplant was compared with the general population by means of standardised incidence ratios (SIR). Cumulative incidence of all cause and cancer related mortality from head and neck keratinocytic was undertaken by a competing risks analysis., Results: A total of 3346 solid organ transplant recipients were identified, 2382 (71.2 %) kidney, 562 (16.8 %) liver, 214 (6.4 %) cardiac and 188 (5.6 %) lung. During the period of follow up of 428 patients developed head and neck cancer, representing (12.8 %) of the population. 97 % of these patients developed keratinocytic cancers, specifically, of head and neck. The frequency of post-transplant head and neck cancer was related to the duration of immunosuppression with 14 % of patients developing cancer at 10 years and 20 % having developed at least one cancer by 15 years. 12 (3 %) patients developed non-cutaneous head and neck malignancy. 10 (0.3 %) patients died due to head and neck keratinocytic malignancy post-transplant. Competing risk analysis demonstrated that organ transplantation conferred a strong independent effect of death, compared to non-transplant patients with head and neck keratinocytes. This applied specifically for kidney (HR 4.4, 95 % CI 2.5-7.8) and heart transplants (HR 6.5, 95 % CI 2.1-19.9), and overall, across the four transplant categories (P < 0.001). The SIR of developing keratinocyte cancer varied based on primary tumor site, gender, and type of transplant organ., Conclusion: Transplant patients demonstrate a particularly high rate of head and neck keratinocyte cancer with a very high rate of associated mortality. Physicians should be cognizant of the increased rate of malignancy in this population and monitor for red flag signs/symptoms., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: To establish unconditional reference centiles for sleep parameters in infants 4-16 weeks of age., Design and Setting: Secondary data analysis of sleep parameters recorded at 4-16 weeks of age in a longitudinal randomised controlled trial (RCT) (BabySMART)., Patients: Healthy term infants assigned to the non-intervention arm of the RCT., Main Outcome Measures: Infants' sleep duration was recorded by parents/guardians daily, from week 2-16 of age using a sleep diary. Reference centiles for total, daytime, night-time and longest sleep episode duration were estimated using multilevel modelling., Results: One hundred and six infants, mean (SD) gestational age of 39.9 (1.2) weeks and mean (SD) birth weight of 3.6 (0.5) kg had sleep recorded contributing 1264 measurements for each sleep parameter. Between 4 and 16 weeks of age total sleep duration in a 24-hour period, night-time sleep duration in a 12-hour period and infant's longest sleep episode duration increased, while daytime sleep duration in a 12-hour period decreased., Conclusions: Reference centiles up to 4 months of age in infants highlight the gradual decrease in daytime sleep and large increases in night-time sleep, which occur in tandem with increasing lengths of sleep episodes. These reference centiles provide useful sleep values for infant sleep trajectory occurring in early life and may be helpful for parents and clinicians., Trial Registration Number: NCT03381027., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Upon the COVID-19 pandemic onset in Ireland, cancer service disruptions occurred due to prioritisation of COVID-19 related care, redeployment of staff, initial pausing of screening, diagnostic, medical and surgical oncology procedures, staff shortages due to COVID-19 infection and impacts on the physical and mental health of cancer healthcare workers. This was coupled with reluctance among people with symptoms suspicious for cancer to attend for clinical evaluation, due to concerns of contracting the virus. This was further compounded by a cyber-attack on national health service IT systems on May 14th 2021. The Irish Cancer Society, a national cancer charity with a role in advocacy, research and patient supports, convened a multi-disciplinary stakeholder group (COVID-19 and Cancer Working Group) to reflect on and understand the impact of the pandemic on cancer patients and services in Ireland, and discuss potential mitigation strategies. Perspectives on experiences were gathered across domains including timeliness of data acquisition and its conversion into intelligence, and the resourcing of cancer care to address cancer service impacts. The group highlighted aspects for future research to understand the long-term pandemic impact on cancer outcomes, while also highlighting potential strategies to support cancer services, build resilience and address delayed diagnosis. Additional measures include the need for cancer workforce recruitment and retention, increased mental health supports for both patients and oncology professionals, improvements to public health messaging, a near real-time multimodal national cancer database, and robust digital and physical infrastructure to mitigate impacts of the current pandemic and future challenges to cancer care systems., Competing Interests: Disclosure/conflict of interest statement All authors have declared that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: To examine associations of assisted reproductive technology (ART) conception (vs. natural conception: NC) with offspring cardiometabolic health outcomes and whether these differ with age., Methods and Results: Differences in systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR), lipids, and hyperglycaemic/insulin resistance markers were examined using multiple linear regression models in 14 population-based birth cohorts in Europe, Australia, and Singapore, and results were combined using meta-analysis. Change in cardiometabolic outcomes from 2 to 26 years was examined using trajectory modelling of four cohorts with repeated measures. 35 938 (654 ART) offspring were included in the meta-analysis. Mean age ranged from 13 months to 27.4 years but was <10 years in 11/14 cohorts. Meta-analysis found no statistical difference (ART minus NC) in SBP (-0.53 mmHg; 95% CI:-1.59 to 0.53), DBP (-0.24 mmHg; -0.83 to 0.35), or HR (0.02 beat/min; -0.91 to 0.94). Total cholesterol (2.59%; 0.10-5.07), HDL cholesterol (4.16%; 2.52-5.81), LDL cholesterol (4.95%; 0.47-9.43) were statistically significantly higher in ART-conceived vs. NC offspring. No statistical difference was seen for triglycerides (TG), glucose, insulin, and glycated haemoglobin. Long-term follow-up of 17 244 (244 ART) births identified statistically significant associations between ART and lower predicted SBP/DBP in childhood, and subtle trajectories to higher SBP and TG in young adulthood; however, most differences were not statistically significant., Conclusion: These findings of small and statistically non-significant differences in offspring cardiometabolic outcomes should reassure people receiving ART. Longer-term follow-up is warranted to investigate changes over adulthood in the risks of hypertension, dyslipidaemia, and preclinical and clinical cardiovascular disease., Competing Interests: Conflict of interest: D.A.L. reported grants from national and international government and charity funders, Roche Diagnostics, and Medtronic Ltd for work unrelated to this publication. S.M.N. reported grants from Roche Diagnostics, Access Fertility, Modern Fertility, Ferring Pharmaceuticals, TFP, and Merck for work unrelated to this publication. The other authors report no conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Protecting the skin barrier in early infancy may prevent atopic dermatitis (AD). We investigated if daily emollient use from birth to 2 months reduced AD incidence in high-risk infants at 12 months., Methods: This was a single-center, two-armed, investigator-blinded, randomized controlled clinical trial (NCT03871998). Term infants identified as high risk for AD (parental history of AD, asthma or allergic rhinitis) were recruited within 4 days of birth and randomised 1:1 to either twice-daily emollient application for the first 8 weeks of life (intervention group), using an emollient specifically formulated for very dry, AD-prone skin, or to standard routine skin care (control group). The primary outcome was cumulative AD incidence at 12 months. AD <6 months was diagnosed based on clinical presence of AD. The UK Working Party Diagnostic Criteria were applied when diagnosing AD between 6 and 12 months., Results: Three hundred twenty-one were randomised (161 intervention and 160 control), with 61 withdrawals (41 intervention, 20 control). The cumulative incidence of AD at 12 months was 32.8% in the intervention group vs. 46.4% in the control group, p = 0.036 [Relative risk (95%CI): 0.707 (0.516, 0.965)]. One infant in the intervention group was withdrawn from the study following development of a rash that had a potential relationship with the emollient. There was no significant difference in the incidence of skin infections between the intervention and control groups during the intervention period (5.0% vs. 5.7%, p > 0.05)., Conclusions: This study has demonstrated that early initiation of daily specialized emollient use until 2 months reduces the incidence of AD in the first year of life in high-risk infants., (© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Objective: To assess if early clinical and electroencephalography (EEG) features predict later seizure development in infants with hypoxic-ischemic encephalopathy (HIE)., Methods: Clinical and EEG parameters <12 h of birth from infants with HIE across eight European Neonatal Units were used to develop seizure-prediction models. Clinical parameters included intrapartum complications, fetal distress, gestational age, delivery mode, gender, birth weight, Apgar scores, assisted ventilation, cord pH, and blood gases. The earliest EEG hour provided a qualitative analysis (discontinuity, amplitude, asymmetry/asynchrony, sleep-wake cycle [SWC]) and a quantitative analysis (power, discontinuity, spectral distribution, inter-hemispheric connectivity) from full montage and two-channel amplitude-integrated EEG (aEEG). Subgroup analysis, only including infants without anti-seizure medication (ASM) prior to EEG was also performed. Machine-learning (ML) models (random forest and gradient boosting algorithms) were developed to predict infants who would later develop seizures and assessed using Matthews correlation coefficient (MCC) and area under the receiver-operating characteristic curve (AUC)., Results: The study included 162 infants with HIE (53 had seizures). Low Apgar, need for ventilation, high lactate, low base excess, absent SWC, low EEG power, and increased EEG discontinuity were associated with seizures. The following predictive models were developed: clinical (MCC 0.368, AUC 0.681), qualitative EEG (MCC 0.467, AUC 0.729), quantitative EEG (MCC 0.473, AUC 0.730), clinical and qualitative EEG (MCC 0.470, AUC 0.721), and clinical and quantitative EEG (MCC 0.513, AUC 0.746). The clinical and qualitative-EEG model significantly outperformed the clinical model alone (MCC 0.470 vs 0.368, p-value .037). The clinical and quantitative-EEG model significantly outperformed the clinical model (MCC 0.513 vs 0.368, p-value .012). The clinical and quantitative-EEG model for infants without ASM (n = 131) had MCC 0.588, AUC 0.832. Performance for quantitative aEEG (n = 159) was MCC 0.381, AUC 0.696 and clinical and quantitative aEEG was MCC 0.384, AUC 0.720., Significance: Early EEG background analysis combined with readily available clinical data helped predict infants who were at highest risk of seizures, hours before they occur. Automated quantitative-EEG analysis was as good as expert analysis for predicting seizures, supporting the use of automated assessment tools for early evaluation of HIE., (© 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Aims: Heart rate variability (HRV) has previously been assessed as a biomarker for brain injury and prognosis in neonates. The aim of this cohort study was to use HRV to predict the electroencephalography (EEG) grade in neonatal hypoxic-ischaemic encephalopathy (HIE) within the first 12 h., Methods: We included 120 infants with HIE recruited as part of two European multi-centre studies, with electrocardiography (ECG) and EEG monitoring performed before 12 h of age. HRV features and EEG background were assessed using the earliest 1 h epoch of ECG-EEG monitoring. HRV was expressed in time, frequency and complexity features. EEG background was graded from 0-normal, 1-mild, 2-moderate, 3-major abnormalities to 4-inactive. Clinical parameters known within 6 h of birth were collected (intrapartum complications, foetal distress, gestational age, mode of delivery, gender, birth weight, Apgar at 1 and 5, assisted ventilation at 10 min). Using logistic regression analysis, prediction models for EEG severity were developed for HRV features and clinical parameters, separately and combined. Multivariable model analysis included 101 infants without missing data., Results: Of 120 infants included, 54 (45%) had normal-mild and 66 (55%) had moderate-severe EEG grade. The performance of HRV model was AUROC 0.837 (95% CI: 0.759-0.914) and clinical model was AUROC 0.836 (95% CI: 0.759-0.914). The HRV and clinical model combined had an AUROC of 0.895 (95% CI: 0.832-0.958). Therapeutic hypothermia and anti-seizure medication did not affect the model performance., Conclusions: Early HRV and clinical information accurately predicted EEG grade in HIE within the first 12 h of birth. This might be beneficial when EEG monitoring is not available in the early postnatal period and for referral centres who may want some objective information on HIE severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Pavel, Mathieson, Livingstone, O' Toole, Pressler, de Vries, Rennie, Mitra, Dempsey, Murray, Marnane, Boylan and ANSeR Consortium.)

Introduction: The SARS-CoV-2 (COVID-19) pandemic was managed with sustained mass lockdowns to prevent spread of COVID-19 infection. Babies born during the early stages of the pandemic missed the opportunity of meeting a normal social circle of people outside the family home., Methods: We compared 10 parentally reported developmental milestones at 12-month assessment in a cohort of 309 babies born at the onset of the pandemic (CORAL cohort) and 1629 babies from a historical birth cohort (BASELINE cohort recruited between 2008 and 2011)., Results: Compared with a historical cohort, babies born into lockdown appeared to have some deficits in social communication. Fewer infants in the pandemic cohort had one definite and meaningful word (76.6% vs 89.3%), could point (83.8% vs 92.8%) or wave bye-bye (87.7% vs 94.4%) at 12-month assessment. Adjusted log-binomial regression analyses demonstrated significant differences in social communication in the CORAL cohort compared with the BASELINE cohort: one definite and meaningful word (relative risk (RR): 0.86 (95% CI: 0.80 to 0.92)), pointing (RR: 0.91 (95% CI: 0.86 to 0.96)) and waving bye-bye (RR: 0.94 (95% CI: 0.90 to 0.99))., Discussion: Parentally reported developmental outcomes in a birth cohort of babies born into lockdown during the COVID-19 pandemic may indicate some potential deficits in early life social communication. It must be noted that milestones are parentally reported and comparison is with a historical cohort with associated limitations. Further studies with standardised testing is required to validate these findings., Conclusion: Pandemic-associated social isolation may have impacted on the social communication skills in babies born during the pandemic compared with a historical cohort. Babies are resilient and inquisitive by nature, and it is hoped that with societal re-emergence and increase in social circles, their social communication skills will improve., Competing Interests: Competing interests: JH is a board member of Clemens Von Pirquet Foundation. No other conflicts declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Maternal mental illness has a significant influence on negative maternal and childhood outcomes. Few studies have focused on both maternal depression and anxiety, or explored the interplay of maternal mental illness and the mother-infant bond. We aimed to examine the relationship between early postnatal attachment and mental illness at 4 and 18 months postpartum., Methods: This was a secondary analysis of 168 mothers recruited from the BabySmart Study. All women delivered healthy term infants. Depression and anxiety symptoms were measured via the Edinburgh Postnatal Depression Scale (EPDS) and Beck's Depression and Anxiety Inventory at 4 and 18 months respectively. Maternal Postnatal Attachment Scale (MPAS) was completed at 4 months. Negative binomial regression analysis investigated associated risk factors at both time points., Results: The prevalence of postpartum depression fell from 12.5% at 4 months to 10.7% at 18 months. Anxiety rates increased from 13.1% to 17.9% at similar time points. At 18 months, both symptoms were new in almost two-thirds of women, 61.1% and 73.3% respectively. There was a strong correlation between the anxiety scale of the EPDS and the total EPDS p-score (R=0.887, p<0.001). Early postpartum anxiety was an independent risk factor for later anxiety and depression. High attachment scores were an independent protective factor for depression at 4 months (RR=0.943, 95%CI: 0.924-0.962, p<0.001) and 18 months (RR=0.971, 95%CI: 0.949-0.997, p=0.026), and protected against early postpartum anxiety (RR=0.952, 95%CI: 0.933-0.97, p<0.001)., Conclusion: The prevalence of postnatal depression at 4 months was similar to national and international rates, although clinical anxiety increased over time with almost 1 in 5 women scoring in the clinical anxiety range at 18 months. Strong maternal attachment was associated with decreased reported symptoms of both depression and anxiety. The effect of persistent maternal anxiety on maternal and infant health needs to be determined.

The application of machine learning (ML) to address population health challenges has received much less attention than its application in the clinical setting. One such challenge is addressing disparities in early childhood cognitive development-a complex public health issue rooted in the social determinants of health, exacerbated by inequity, characterised by intergenerational transmission, and which will continue unabated without novel approaches to address it. Early life, the period of optimal neuroplasticity, presents a window of opportunity for early intervention to improve cognitive development. Unfortunately for many, this window will be missed, and intervention may never occur or occur only when overt signs of cognitive delay manifest. In this review, we explore the potential value of ML and big data analysis in the early identification of children at risk for poor cognitive outcome, an area where there is an apparent dearth of research. We compare and contrast traditional statistical methods with ML approaches, provide examples of how ML has been used to date in the field of neurodevelopmental disorders, and present a discussion of the opportunities and risks associated with its use at a population level. The review concludes by highlighting potential directions for future research in this area. IMPACT: To date, the application of machine learning to address population health challenges in paediatrics lags behind other clinical applications. This review provides an overview of the public health challenge we face in addressing disparities in childhood cognitive development and focuses on the cornerstone of early intervention. Recent advances in our ability to collect large volumes of data, and in analytic capabilities, provide a potential opportunity to improve current practices in this field. This review explores the potential role of machine learning and big data analysis in the early identification of children at risk for poor cognitive outcomes., (© 2022. The Author(s).)

Background: The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years of diagnosis and provide new analytical perspectives on estimates of long-term survival and the cured fraction of patients with childhood cancer., Methods: In this population-based study, we analysed 135 847 children (aged 0-14 years) diagnosed during 2000-13 and followed up to the end of 2014, recruited from 80 population-based cancer registries in 31 European countries. We calculated age-adjusted 5-year survival differences by country and over time using period analysis, for all cancers combined and for major cancer types. We applied a variant of standard mixture cure models for survival data to estimate the cure fraction of patients by childhood cancer and to estimate projected 15-year survival., Findings: 5-year survival for all childhood cancer combined in Europe in 2010-14 was 81% (95% CI 81-82), showing an increase of three percentage points compared with 2004-06. Significant progress over time was observed for almost all cancers. Survival remained stable for osteosarcomas, Ewing sarcoma, Burkitt lymphoma, non-Hodgkin lymphomas, and rhabdomyoscarcomas. For all cancers combined, inequalities still persisted among European countries (with age-adjusted 5-year survival ranging from 71% [95% CI 60-79] to 87% [77-93]). The 15-year survival projection for all patients with childhood cancer diagnosed in 2010-13 was 78%. We estimated the yearly long-term mortality rate due to causes other than the diagnosed cancer to be around 2 per 1000 patients for all childhood cancer combined, but to approach zero for retinoblastoma. The cure fraction for patients with childhood cancer increased over time from 74% (95% CI 73-75) in 1998-2001 to 80% (79-81) in 2010-13. In the latter cohort, the cure fraction rate ranged from 99% (95% CI 74-100) for retinoblastoma to 60% (58-63) for CNS tumours and reached 90% (95% CI 87-93) for lymphoid leukaemia and 70% (67-73) for acute myeloid leukaemia., Interpretation: Childhood cancer survival is increasing over time in Europe but there are still some differences among countries. Regular monitoring of childhood cancer survival and estimation of the cure fraction through population-based registry data are crucial for evaluating advances in paediatric cancer care., Funding: European Commission., Competing Interests: Declaration of interests AC reports consulting fees from EUSA PHARMA outside of the submitted work. All others authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To describe early, continuous, non-invasive measures of cardiac output (CO) and evolution over time in infants with hypoxic-ischaemic encephalopathy (HIE)., Study Design: Prospective observational study of 44 infants with HIE (23 mild, 17 moderate, 4 severe) and 17 term controls. Infants with HIE had non-invasive CO monitoring (NICOM) continuously in the neonatal unit. Term controls had NICOM recorded at 6 and 24 h. A mixed-modelling approach was used to assess change in CO over time by group., Results: Infants with moderate HIE have significantly lower CO than the mild group at all timepoints (10.7 mls/kg/min lower, 95% CI:1.0,20.4, p = 0.03) which increases over time, driven by a gradual increase in stroke volume (SV). CO increased further during rewarming predominantly due to an increase in HR., Conclusion: TH has a significant impact on HR but SV appears largely unaffected. NICOM may provide a non-invasive, continuous, low-cost alternative to monitoring CO in infants with HIE however further research is warranted., (© 2022. The Author(s).)

Objectives: In this study, we applied the random forest (RF) algorithm to birth-cohort data to train a model to predict low cognitive ability at 5 years of age and to identify the important predictive features. Methods: Data was from 1,070 participants in the Irish population-based BASELINE cohort. A RF model was trained to predict an intelligence quotient (IQ) score ≤90 at age 5 years using maternal, infant, and sociodemographic features. Feature importance was examined and internal validation performed using 10-fold cross validation repeated 5 times. Results The five most important predictive features were the total years of maternal schooling, infant Apgar score at 1 min, socioeconomic index, maternal BMI, and alcohol consumption in the first trimester. On internal validation a parsimonious RF model based on 11 features showed excellent predictive ability, correctly classifying 95% of participants. This provides a foundation suitable for external validation in an unseen cohort. Conclusion: Machine learning approaches to large existing datasets can provide accurate feature selection to improve risk prediction. Further validation of this model is required in cohorts representative of the general population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bowe, Lightbody, Staines, Kiely, McCarthy and Murray.)

Introduction: To capture the patient's attitude toward remote monitoring of motor neuron disease (MND) in care and clinical trials, and their concerns and preferences regarding the use of digital technology., Methods: We performed an international multi-centre survey study in three MND clinics in The Netherlands, the United Kingdom, and Australia. The survey was co-developed by investigators and patients with MND, and sent to patients by e-mail or postal-mail. The main topics included: patients' attitude towards remote care, participating in decentralized clinical trials, and preferences for and concerns with digital technology use., Results: In total, 332 patients with MND participated. A majority of patients indicated they would be happy to self-monitor their health from home (69%), be remotely monitored by a multidisciplinary care team (75%), and would be willing to participate in clinical trials from home (65%). Patients considered respiratory function and muscle strength most valuable for home-monitoring. The majority of patients considered the use of at least three devices/apps (75%) once a week (61%) to be acceptable for home-monitoring. Fifteen percent of patients indicated they would not wish to perform home-measurements; reporting concerns about the burden and distress of home-monitoring, privacy and data security., Conclusion: Most patients with MND exhibited a positive attitude toward the use of digital technology in both care and clinical trial settings. A subgroup of patients reported concerns with home-monitoring, which should be addressed in order to improve widespread adoption of remote digital technology in clinical MND care., (© 2022. The Author(s).)

Background: Atopic dermatitis (AD) has a strong genetic basis. The objective of this study was to assess the association between parental atopy and AD development by 2 years., Methods: A secondary data analysis of the BASELINE Birth Cohort study was performed (n = 2183). Parental atopy was self-reported at 2 months. Infants were examined for AD by trained health care professionals at 6, 12, and 24 months. Variables extracted from the database related to skin barrier function, early skincare, parental atopy, and AD. Statistical analysis adjusted for potential confounding variables., Results: Complete data on AD status were available for 1505 children at 6, 12, and 24 months. Prevalence of AD was 18.6% at 6 months, 15.2% at 12 months, and 16.5% at 24 months. Adjusted odds ratios (95% CIs) following multivariable analysis were 1.57 (1.09-2.25) at 6 months and 1.66 (1.12-2.46) at 12 months for maternal AD; 1.90 (1.28-2.83) at 6 months and 1.85 (1.20-2.85) at 24 months for paternal AD; 1.76 (1.21-2.56) at 6 months and 1.75 (1.16-2.63) at 12 months for maternal asthma; and 1.70 (1.19-2.45) at 6 months, 1.86 (1.26-2.76) at 12 months, and 1.99 (1.34-2.97) at 24 months for paternal asthma. Parental rhinitis was only associated with AD with maternal rhinitis at 24 months (aOR (95% CI): 1.79 (1.15-2.80))., Conclusion: Parental AD and asthma were associated with increased risk of objectively diagnosed AD in offspring in this contemporary cohort., (© 2022 The Authors. Pediatric Dermatology published by Wiley Periodicals LLC.)

Aim: To describe early cerebral oxygenation (cSO 2 ) and fractional tissue oxygen extraction (FTOE) values and their evolution over the first days of life in infants with all grades of hypoxic-ischaemic encephalopathy (HIE) and to determine whether cSO 2 and FTOE measured early (6 and 12 h) can predict short-term outcome., Methods: Prospective, observational study of cerebral near-infrared spectroscopy (NIRS) in infants >36 weeks' gestation with HIE. Ten one-hour epochs of cSO 2 and FTOE were extracted for each infant over the first 84 h. Infants with moderate and severe HIE received therapeutic hypothermia (TH). Abnormal outcome was defined as abnormal magnetic resonance imaging (MRI) and/or death., Results: Fifty-eight infants were included (28 mild, 24 moderate, 6 severe). Median gestational age was 39.9 weeks (IQR 38.1-40.7) and birthweight was 3.35 kgs (IQR 2.97-3.71). cSO 2 increased and FTOE decreased over the first 24 h in all grades of HIE. Compared to the moderate group, infants with mild HIE had significantly higher cSO 2 at 6 h (p = 0.003), 9 h (p = 0.009) and 12 h (p = 0.032) and lower FTOE at 6 h (p = 0.016) and 9 h (0.029). cSO 2 and FTOE at 6 and 12 h did not predict abnormal outcome., Conclusion: Infants with mild HIE have higher cSO 2 and lower FTOE than those with moderate or severe HIE in the first 12 h of life. cSO 2 increased in all grades of HIE over the first 24 h regardless of TH status., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Over 19,000 residents and health-care workers in 315 RCFs were swabbed in a once - off mass swabbing of residents and staff in residential care facilities (RCFs) in the Cork/Kerry region in Ireland in April and May 2020. This exercise was in response to epidemiological evidence demonstrating increasing community transmission of COVID-19 and emerging evidence of the vulnerability of older persons, particularly those with underlying medical conditions. The effectiveness of such strategies is uncertain and may depend on both the positive case yield and efficiency of testing turn-around to ensure that timely control measures are put in place. The overall positivity rate was 0.88% (n = 172). Mass swabbing allowed early identification of some new cases and outbreaks in RCFs. This facilitated early public health interventions to protect the most vulnerable members of society.

Objective: Examine the association between alcohol consumption before and during pregnancy and neurodevelopmental outcomes in the offspring at two and five years., Study Design: Retrospective analysis of a prospective longitudinal cohort; SCOPE-BASELINE. Data on pre-conception and prenatal alcohol consumption were obtained at 15 weeks' gestation and categorised as abstinent, occasional-low (1-7units/week) and moderate-heavy (≥8units/week). Binge drinking was defined as ≥6 units/session. Outcome measures (Child Behaviour Checklist and Kaufman Brief Intelligence Test) were obtained at two and five years. Linear regression examined an alcohol consumption and Child Behaviour Checklist and Kaufman Brief Intelligence Test relationship, adjusting for several potential confounders., Results: Data on alcohol consumption was available for 1,507 women. Adjusted linear regression suggested few associations: pre-pregnancy occasional-low alcohol consumption was associated with lower log externalizing Child Behaviour Checklist scores (-0.264, 95% CI: -0.009, -0.520), while pre-pregnancy moderate-high levels of alcohol consumption was associated with lower Kaufman Brief Intelligence Test verbal standard scores (-0.034, 95% CI: -0.001, -0.068) and composite IQ scores (-0.028, 95% CI: -0.056, -0.0004) at five-years. In the first trimester, moderate-high levels of alcohol consumption was associated with lower internalizing Child Behaviour Checklist scores at two-years (-0.252, 95% CI: -0.074, -0.430). No significant associations were observed between number of binge episodes pre-pregnancy or binge drinking in the first trimester and Child Behaviour Checklist or Kaufman Brief Intelligence Test., Conclusions: We did not find strong evidence of associations between pre-pregnancy and early pregnancy maternal alcohol consumption and adverse neurodevelopmental outcomes at age two and five years overall. Further research examining alcohol consumption (including binge drinking) beyond 15 weeks' gestation and subsequent neurodevelopmental outcomes is needed to examine the potential effect of alcohol consumption in later pregnancy., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population., Objective: To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study., Design, Setting, and Participants: This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022., Exposures: Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction)., Main Outcomes and Measures: The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups., Results: Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units)., Conclusions and Relevance: These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

Background: Atopic dermatitis (AD) is the most common chronic inflammatory skin condition in childhood. Most (50-60%) children with AD report sleep disturbance, which is secondary to itch, dry skin, inflammation, and abnormal circadian rhythm. Sleep is essential for brain development, learning, and growth. Sleep disruption in early life is associated with cognitive and psychological dysfunction in later life. The aim of this study is to describe in detail the sleep architecture of infants with early-onset atopic dermatitis (AD), compared to controls, by using EEG polysomnography, sleep actigraphy, and parental reporting., Methods: This observational study will recruit six- to eight-month old infants with moderate to severe AD and age-matched control infants who do not have AD. At six-eight months diurnal sleep electroencephalography and polysomnography will be performed in our research center. Nocturnal sleep actigraphy will be performed at home for five consecutive nights at six-eight months and 12 months. Between six and 12 months, monthly questionnaires will capture data on quantitative sleep and parental sleep. Skin barrier and immune profiles will be captured at six-eight and 12 months. AD will be assessed using standardized severity assessment tools and treated according to protocol. A neurodevelopmental assessment will be performed at 18 months to assess cognition and behaviour. An estimated sample size of 50 participants in each group is required to power the primary outcome of disturbed macrostructure of sleep and secondary outcomes of disturbed microstructure of sleep, and disturbed parental sleep, assuming an attrition rate of 60%. Potential confounding factors which will be controlled for in the data analysis will include parental educational level, parental depression, feeding practice, and number of siblings., Discussion: This study will provide a rich analysis of sleep in infants with AD in the first year of life using detailed electroencephalography, novel actigraphy techniques, and longitudinal parent-reported data. It may provide guidance on the optimal treatment of AD to prevent or reduce sleep disruption., Trial Registration: clinicaltrials.gov NCT05031754 , retrospectively registered on September 2nd, 2021., (© 2022. The Author(s).)

Aim: This retrospective, longitudinal study examined the predictive value of the ages and stages questionnaire (ASQ) in late infancy for identifying children who progressed to have low cognitive ability at 5 years of age., Methods: The ASQ was performed on 755 participants from the Irish BASELINE birth cohort at 24 or 27 months of age. Intelligence quotient was measured at age 5 with the Kaufmann Brief Intelligence Test, Second Edition, and low cognitive ability was defined as a score more than 1 standard deviation below the mean. The ASQ's predictive value was examined, together with other factors associated with low cognitive ability at 5 years., Results: When the ASQ was performed at 24 or 27 months, the overall sensitivity for identifying low cognitive ability at 5 years was 20.8% and the specificity was 91.1%. Using a total score cut-off point increased the sensitivity to 46.6% and 71.4% at 24 and 27 months, but specificity fell to 74.1% and 67.2%, respectively. After adjusting for ASQ performance, maternal education and family income were strongly associated with cognitive outcomes at 5 years., Conclusion: The ASQ did not detect the majority of children with low cognitive ability at age 5. Alternative methods need investigation., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)